Herb-induced Liver Injury Research Articles

P.001: Herb-induced liver injury: General approach and herbs likely to cause liver injury in Turkey.

P.001: Herb-induced liver injury: General approach and herbs likely to cause liver injury in Turkey.

Successful corticosteroid therapy for severe liver injury secondary to herbal traditional Chinese medicine, Mega Defends X, assessed for causality by the updated RUCAM: A case report.

In China, herbal traditional Chinese medicine products are readily obtained without any requirement of prescription and widely used in real life, thereby increasing the incidence of their related herb-induced liver injury (HILI). However, the diagnosis of HILI is still challenging because its clinical manifestations are variable due to lack of any specific biomarkers. Misdiagnosis and inappropriate treatment may result in the progression of HILI. A 55-year-old female patient was admitted to the hospital due to progressive jaundice. The diagnoses of HILI secondary to Mega Defends X, an herbal traditional Chinese medicine product, for which the score was 9 based on the updated Roussel Uclaf Causality Assessment Method of 2016. The patient received corticosteroid with a stepwise dosage reduction. The liver injury significantly improved by corticosteroid treatment. Corticosteroids should be potentially effective and safe in patients with severe HILI.

Challenges in herbal-induced liver injury identification and prevention.

Herbal and dietary supplements (HDS) are being used worldwide at an increasing rate. Mirroring this trend, HDS-induced liver injury, also known as HDS-induced liver injury (HILI), has increased significantly over the past three decades in the Drug-Induced Liver Injury Network (DILIN), now accounting for 20% of cases of drug-induced liver injury (DILI). There are significant challenges in the identification and prevention of HILI due to varying presentations, ability to make clear diagnosis, identification of the responsible ingredient, lack of treatment, and lack of regulatory oversight of HDS products to confirm their ingredients and ensure safety. The major implicated agents include anabolic steroids, green tea extract, garcinia cambogia, kratom, ashwagandha, turmeric and multi-ingredient nutritional supplements. Fortunately, with the formation of major DILI consortiums across the world, the last decade has seen advances in the identification of at-risk genetic phenotypes, the use of chemical analysis on multi-ingredient nutritional supplements, and the publication of data/injury patterns of potentially risky HDS.

A Hidden Cause of Hypertransaminasemia: Liver Toxicity Caused by Chelidonium Majus L.: Report of Two Cases of Herb-Induced Liver Injury and Literature Review.

In instances where individuals manifest elevated transaminase levels without a clearly discernible cause, a comprehensive patient history proves invaluable in unveiling latent triggers. In this report, we present 2 cases of herb-induced liver injury (HILI) characterized by severe hypertransaminasemia attributed to the consumption of Chelidonium majus L. (also known as greater celandine [GC]), an agent considered an alternative therapeutic remedy. Exploring the occurrence and range of clinical manifestations in HILI linked to Chelidonium majus L., while also investigating the potential triggers and predisposing factors for hepatotoxic reactions post Chelidonium majus L. usage, remains challenging due to the absence of definitive laboratory tests to identify the causative agent. Two case reports were detailed, and a systematic literature review using PubMed was conducted including published literature till March 2023. Moreover, a manual search of reference lists of pertinent articles was performed to identify any additional relevant missed publications. In the first case, a 64-year-old woman presented with jaundice, revealing a 1-month history of using GC capsules to manage gallstones. Diagnostic assessment identified HILI, gallstones, and choledocolithiasis, with transaminase levels exceeding 1000 IU/L. After discontinuing GC and receiving intravenous therapy with amino acids and phospholipids, the patient's condition significantly improved. Subsequently, she underwent endoscopic common bile duct stone removal and cholecystectomy. In the second case, a 66-year-old woman presented with elevated liver function test results discovered incidentally during musculoskeletal pain evaluation. Upon further questioning, the patient disclosed regular consumption of GC tea for "health promotion." Following intravenous therapy using amino acids and phospholipids, her transaminase levels returned to normal. The literature review identified 38 cases of HILI associated with GC preparations, primarily in adult women aged 27-77 years, with a predominant reporting location in Germany. Various forms of GC were used, with treatment durations ranging from 1 week to a year. Discontinuation of GC generally led to recovery in these cases. Chelidonium majus L., a potent herb often used in alternative medicine, has significant hepatotoxic potential, requiring physicians to be vigilant in cases of unexplained liver injury.

Herb induced liver injury by Xianling Gubao Tablets: A case assessed for causality using updated RUCAM and integrated evidence chain

ObjectiveA typical case of Xianling Gubao (XLGB) Tablets-induced liver injury was systematically studied in the clinic and the laboratory. MethodsA patient with herb-induced liver injury (HILI) and a history of taking XLGB Tablets before disease onset was engaged as the study subject, and the case was diagnosed according to the updated Roussel Uclaf Causality Assessment Method (RUCAM) and the integrated evidence chain (iEC) method recommended by the Guidelines for Diagnosis and Treatment of Herb-induced Liver Injury (HILI Guidelines). ResultsClinical history, biochemical indexes and imaging tests were used to exclude the influence of fundamental diseases and confusing liver diseases such as viral, alcoholic and autoimmune liver diseases on the diagnosis. Based on an investigation of the patient’s medication history, she was suspected to have HILI caused by XLGB Tablets, as the patient was only taking an oral preparation of XLGB Tablets, and the influence of other drugs on the diagnosis was excluded. This patient with alanine aminotransferase (ALT) ≥ 3 × upper limit of normal (ULN) and a calculated R of 6 was diagnosed with possible acute drug-induced hepatocellular injury. The relationship was considered “highly probable” (score of 9) using the updated RUCAM of 2016. Moreover, the fingerprint similarity between the preparation taken by the patient and a commercially available preparation was 0.99, suggesting that the patient was consuming XLGB Tablets rather than another drug. LC-MS technology and the Agilent Fake TCM-Drugs database were used to investigate the drug, and no chemical additions were found. Examination of the drug for pesticide residues, heavy metals, aflatoxins and other exogenous substances indicated compliance with the content limits of the Chinese Pharmacopoeia. ConclusionIn summary, the final diagnosis of XLGB-induced liver injury reached the clinical diagnosis of HILI and was acute severe hepatocellular injury type by the updated RUCAM and iEC. Therefore, this study provides scientific evidence regarding the causality evaluation of compound preparations of traditional Chinese medicines-induced liver injury.

Herbal- and Dietary-Supplement-Induced Liver Injury: A Review of the Recent Literature

Herbal-induced liver injury (HILI) continues to increase in prevalence each year due to the ongoing popularity of herbal supplements and complementary and alternative medicines. A detailed literature review of case reports and clinical studies published from March 2021 to March 2023 was performed. We discuss the epidemiology and diagnosis of HILI as well as the current and proposed laws and regulations. The 2021 ACG guidelines and 2022 AASLD practice guidelines for the diagnosis and management of drug and herbal-induced liver injury are discussed. We describe updates to previously reported etiologies of HILI such as ayurveda, ashwagandha, turmeric, kratom, green tea extract, and garcinia cambogia. Newly described supplements resulting in HILI, such as tinospora cordifolia, horse chestnut, alkaline water, and more, are described. We discuss newly and previously identified hepatoprotective herbal supplements as they have been reported in the study of animal models and human liver cells. This review suggests the need for ongoing research on the causes and mechanisms of HILI to ensure its proper diagnosis, prevention, and treatment in the future. The goal of this review is to provide novice and expert readers with knowledge regarding the possible etiologies of HILI and a general overview.

Steroid-responsive intractable pruritus in drug-induced liver injury: a case series

Background: Drug-induced liver injury (DILI) is commonly caused by modern medications, complementary and alternative medicines (CAMs), and other toxins. DILI is an umbrella term encompassing herb-induced liver injury (HILI) caused by herbs and CAMs, in addition to other medications. Apart from the cessation of the culprit drug and the supportive management, there are no definite treatment options for DILI. Although being used in DILI, steroids are not the standard medications for DILI, except that they are indicated for a few specific conditions. Materials and Methods: We report five cases of DILI with pruritus who responded well to steroids used as rescue therapy. DILI in these five cases was caused by CAMs (1), anabolic steroids (2), dapsone (1), and antifungal drug itraconazole (1). All patients presented with jaundice and pruritus, and their conditions did not improve following the discontinuation of offending agents and the implementation of supportive care. We used the Roussel UCLAF Causality Assessment Method 2016 for causality assessment. R-value was used to describe the pattern of liver injury. All patients underwent comprehensive work-up including liver biopsy as part of the procedure to rule out other potential etiologies. Steroids were used as a last resort, and both clinical and biochemical measurements were conducted. Results: The mean age of patients was 28.8 years, and the majority of them were males (80%). The median duration from symptom onset to presentation at our hospital was 4 weeks. The mean durations for pruritus improvement and complete biochemical improvement after steroid treatment were 3.2 weeks and 11.2 weeks, respectively. Extended follow-up was done for a mean period of 29.6 weeks from symptom presentation, and none of the patients had recurrence of liver injury after discontinuation of steroids. Conclusions: Ssteroids can be used to treat as rescue therapy for severe DILI with intractable pruritus in patients with worsening liver function. Relevance for Patients: DILI in selected cases can be therapeutically managed using steroids, which, however, should not be indicated as a first-line treatment.

S3539 Herb-Induced Liver Injury Due to Ashwagandha: Unique Cases With Different Liver Injury Patterns

S3539 Herb-Induced Liver Injury Due to Ashwagandha: Unique Cases With Different Liver Injury Patterns

Isomaculosidine facilitates NLRP3 inflammasome activation by promoting mitochondrial reactive oxygen species production and causes idiosyncratic liver injury

Ethnopharmacological relevanceDictamnus dasycarpus Turcz. (Dictamni Cortex, DC), a Chinese herbal medicine, is commonly used for treating chronic dermatosis and rheumatism, but can also cause herb-induced liver injury (HILI). Our study has demonstrated that DC can induce idiosyncratic HILI, but the mechanism remains unknown. The NLRP3 inflammasome has become a major target for addressing many diseases. The activation of NLRP3 inflammasome is responsible for many liver-related inflammatory diseases, including idiosyncratic HILI. Aim of the studyThe objective of our study was to demonstrate the mechanism underlying the idiosyncratic HILI induced by DC and clarify the susceptible component in DC. Materials and methodsBone marrow-derived macrophages (BMDMs) and THP1 cells were selected to assess the effect of isomaculosidine (IMD) on NLRP3 inflammasome activation in vitro. Western blot, ELISA and Caspase-Glo® 1 Inflammasome Assay, flow cytometry and Immunofluorescence were employed to detect the mechanism of IMD on NLRP3 inflammasome activation. To assess the efficacy of IMD in vivo, mice were intravenously administrated with LPS and then IMD were injected intraperitoneally for 6 h. ResultsThe results of our in vitro studies demonstrate that IMD, the major constituent of DC, specifically promoted ATP- and nigericin-induced activation of NLRP3 inflammasome, but not NLRC4 and AIM2 inflammasomes. Additionally, IMD promoted nigericin-induced ASC oligomerization. Notably, synergistic induction of mtROS played a key role on the activation of NLRP3 inflammasome. IMD increased the mtROS production in the activation of NLRP3 inflammasome induced by nigericin. In addition, the results of our in vivo study showed that the combination of nonhepatotoxic doses of LPS and IMD can increase the levels of ALT, AST, and DBIL, leading to liver injury. ConclusionsIMD specifically facilitated the activation of NLRP3 inflammasome induced by nigericin and ATP, which is responsible for DC-induced idiosyncratic HILI.

New Insights into Herb-Induced Liver Injury.

Significance: Herbs are widely used worldwide. However, inappropriate use of some of the herbs can lead to herb-induced liver injury (HILI). Intriguingly, HILI incidents are on the rise, and our understanding of the underlying etiologies is in progress, and hence, an update on the current status of incidents as well as our understanding on the etiologies of HILI is appropriate. Recent Advances: HILI reports due to the use of some herbs that are traditionally considered to be safe are also on the rise. Furthermore, HILI due to the use of certain herbs in combination with other herbs (herb-herb interaction [HHI]) or non-herb components (herb-drug interaction [HDI]) has also been reported, suggesting a potentially important new type of inappropriate use of herbs. Critical Issues: Updated overviews focus on the epidemiology, etiology, phenotypes, and risk factors of HILI, as well as HDI and HHI, and analysis on several types of newly reported "toxic" effects of herbs based on types of hepatotoxicity and the HILI mechanisms. Future Directions: HILI will continue to be a significant public health challenge in the near future. In the light of the lack of broadly available guidelines and regulations for proper and safe uses of herbs worldwide, raising the public awareness of HILI will remain one of the most effective measures. In particular, it should include a better understanding of the contributing factors; a more detail subclassification and description of HILI, better characterization of the components/substances that could induce HILI; and development of HILI diagnosis based on the Roussel Uclaf Causality Assessment Method (RUCAM). Antioxid. Redox Signal. 38, 1138-1149.

Psoraleae Fructus Ethanol Extract Induced Hepatotoxicity via Impaired Lipid Metabolism Caused by Disruption of Fatty Acid β-Oxidation.

Herb-induced liver injury (HILI) is gradually increasing, and Psoraleae Fructus (PF) has been reported to induce hepatotoxicity. However, its underlying toxicity mechanism has been only poorly revealed. In this paper, we attempted to explore the liver injury and mechanism caused by Psoraleae Fructus ethanol extract (PFE). First, we administered PFE to mice for 4 weeks and evaluated their serum liver function indices. H&E staining was performed to observe the pathological changes of the livers. Oil red O staining was used to visualize hepatic lipids. Serum-untargeted metabolomics and liver proteomics were used to explore the mechanism of PF hepatotoxicity, and transmission electron microscopy was determined to assess mitochondria and western blot to determine potential target proteins expression. The results showed that PFE caused abnormal liver biochemical indicators and liver tissue injury in mice, and there was substantial fat accumulation in liver tissue in this group. Furthermore, metabolomic analysis showed that PFE changed bile acid synthesis, lipid metabolism, etc., and eight metabolites, including linoleic acid, which could be used as potential biomarkers of PFE hepatotoxicity. Proteomic analysis revealed that differential proteins were clustered in the mitochondrial transmembrane transport, the long-chain fatty acid metabolic process and purine ribonucleotide metabolic process. Multiomics analysis showed that eight pathways were enriched in both metabolomics and proteomics, such as bile secretion, unsaturated fatty acid biosynthesis, and linoleic acid metabolism. The downregulation of SLC27A5, CPT1A, NDUFB5, and COX6A1 and upregulation of cytochrome C and ABCC3 expressions also confirmed the impaired fatty acid oxidative catabolism. Altogether, this study revealed that PFE induced hepatotoxicity by damaging mitochondria, reducing fatty acid β-oxidation levels, and inhibiting fatty acids ingested by bile acids.

Green Tea Consumption Is Increasing but There Are Significant Hepatic Side Effects

Herbal medicines including teas and plant extracts have been in use for thousands of years. There are reports of the use of herbal preparations in Egypt, China, India, and Samaria. Many patients consider “natural” herbal teas to be completely free of unwanted side effects. Many herbal products, however, have biological activities that can result in severe hepatic cell toxicity or interact with other herbal products or prescription medications. Their use is increased dramatically. The most common herbal teas and nonmineral natural products are used as self-medication, principally for health improvement. However, these products are potentially dangerous to some individuals. Monitoring for liver injury is an important aspect of drug and herbal safety assessment. When present, herbal-induced liver injury (HILI) may limit the use or result in the discontinuation of these agents. HILI can exhibit with a wide spectrum of clinical and laboratory manifestations, ranging from asymptomatic elevations in aminotransferases to acute liver failure. Most cases of HILI resolve within several weeks after herbal remedy discontinuation. However, some cases can persist as low-level aminotransferase elevations. Our review aims to (1) describe the possible significant discrepancies between the ingredients listed on the label and the actual contents of the preparation; (2) evaluate teas containing multiple plants or herbs which may be adulterated by more toxic herbs, heavy metals, microbials, pharmaceuticals, and medicines; (3) describe pathophysiologic events in herbal tea-induced hepatotoxicity; and (4) discuss the key elements required for attributing the consumption of tea to the induction of liver injury. The widespread use of mixed heterogeneous remedies and the lack of randomized trials are an obstacle to providing safe use of plant-derived teas.

LIVER INJURY INDUCED BY HERBAL AND DIETARY SUPPLEMENTS: A POOLED ANALYSIS OF CASE REPORTS.

The intake of dietary supplements and medicinal plants is very popular worldwide. However, these products are not innocuous, and their intake can cause severe damage to health, especially liver injury. This study aims to describe the clinical cases of dietary supplements-induced liver injury (DSILI) and herb-induced liver injury (HILI), identifying the main products involved and the clinical outcomes related to them. A literature search was performed in PubMed, EMBASE, Google Scholar, and LILACS databases, using the search terms: "Chemical and Drug-Induced Liver Injury", "Dietary Supplements" and "Herbal" and their synonyms. 189 articles were included in the study, totaling 428 clinical cases of drug-induced liver injury. The most frequent agents of liver injury were Herbalife® products, associated with 50 cases, Polygonum multiflorum, with 25 cases, Hydroxycut® products, and green tea, both associated in 19 cases, and Oxyelite Pro® and kava tea, both associated with 16 cases. Most individuals required hospitalization (82.6%) and an important number of cases evolved to death (3.6%), liver transplantation (8.9%), or chronic liver disease (1.9%). The indiscriminate use of dietary supplements and herbal products was associated with an alarming number of cases of liver injury. The mechanisms through which each of the products causes liver damage still need to be better understood, but this review is a warning about the risk associated with the use of products considered harmless by a large part of the population.

S3072 Liver Injury Caused by a Weight Loss Supplement Containing Green Tea Extract and Garcinia Cambogia

Introduction: Herbal-induced liver injury (HILI) is a growing topic worldwide, and herbal and dietary supplements (HDS) are the second leading class of compounds after antimicrobials causing liver injury in the United States. It is thought that many cases go unrecognized, as patients fail to mention their use of HDS. This is a case of mild liver injury in a young woman after taking a short course of a weight loss supplement containing a garcinia cambogia (GC) and green tea extract (GTE). Case Description/Methods: A 45-year-old female with a history of obesity presented to clinic with elevated liver enzymes identified on routine labs from two weeks prior. Medication reconciliation revealed that one month prior, she started a 15-day course of Revert 10.0 by Natureal for weight loss. She stopped taking the supplement on her own as she felt it was not helpful. Her only prescription medication was her oral contraceptive pill. She was born in the United States and denied any prior history of liver disease. She was asymptomatic with no nausea, abdominal pain, or jaundice. Her physical exam was unremarkable. Baseline laboratory values from six months prior showed AST 18 U/L (normal < 40), ALT 14 U/L (normal < 32), ALP 76 U/L (normal 39-117), TBili 0.4 mg/dL (normal < 1.2). Her liver tests after one week of using Revert 10.0 revealed elevations of AST to 49 and ALT to 83, with normal ALP 61, and TBili 0.2. LFTs after two weeks showed further rises in AST to 66, and ALT to 112, with normal ALP 66, and TBili 0.2. Her viral hepatitis panel was non-reactive. An abdominal ultrasound and CT scan of the abdomen/pelvis showed no abnormalities with normal echogenicity and liver morphology. Two weeks after withdrawing the supplement, her LFTs had returned to normal, AST 24, ALT 26, ALP 72, and TBili 0.2. (Figure) Discussion: This is the first report of liver injury from Revert 10.0. We encourage clinicians to consider HILI in patients with even mild laboratory abnormalities, and to conduct thorough history-taking. While GC and GTE are both known hepatotoxins, there are no cases reported of the two agents working in conjunction to cause HILI. Furthermore, the Roussel Uclaf Causality Assessment Method, the gold standard for HILI diagnosis does not consider the potential for synergy between multiple known hepatotoxic agents. Our case highlights that further research should explore how synergy of multiple supplements can affect presentation of HILI.Figure 1.: Liver Enzyme Trend Over Time

Drug-induced Liver Injury and Herb-induced Liver Injury Targeting Key Issues

Abstract: The International Journal of Gastroenterology and Hepatology Diseases starts with a new section on drug induced liver injury (DILI) and herb induced liver injury (HILI), and as its section editor, I would appreciate receiving submissions from potential authors. Closely connected with these forms of liver injury are topics of pathophysiology, clinical features, risk factors on the side of patients as well as drugs or herbs, diagnostic approaches including causality assessment using the updated RUCAM (Roussel Uclaf Causality Assessment Method), and treatment modalities that help reduce risks of acute liver failure, liver transplantation, and lethal outcome. In conclusion, this new section on DILI and HILI will hopefully provide additional insights into the issues related to DILI and HILI.

Identification of intrinsic hepatotoxic compounds in Polygonum multiflorum Thunb. using machine-learning methods

Ethnopharmacological relevancePolygonum multiflorum Thunb. (PM) is a herb, extracts of which have been used as Chinese medicine for years. Although it is believed to be beneficial to the liver, heart, and kidneys, it causes idiosyncratic drug-induced liver injury (DILI). Aim of the studyWe propose that the intrinsic DILI caused by natural products in PM (NPPM) is an important complementary mechanism to PM-related herb-induced liver injury, and aim to identify the ingredients with high DILI potential by machine learning methods. Materials and methodsOne hundred and ninety-seven NPPM were collected from the literature to identify the intrinsic hepatotoxic compounds. Additionally, a DILI-labeled dataset consisting of 2384 compounds was collected and randomly split into training and test sets. A diparametric optimization method was developed to tune the parameters of extended-connectivity fingerprints (ECFPs), Rdkit, and atom-pair fingerprints as well as those of machine-learning (ML) algorithms. Subsequently, K means were employed to cluster the NPPM that were predicted to have a high DILI risk. An in vitro cell-viability assay was performed using HepaRG cells to validate the prediction results. ResultsECFPs with the top 35% of features ranked by the F-value with support vector machine (SVM) yielded the best performance. The optimized SVM model achieved an accuracy of 0.761 and recall value of 0.834 on the test dataset. The silico screening for NPPM resulted in 47 ingredients with high DILI potential, which were clustered into six groups based on the elbow method. A representative subgroup that contained 21 ingredients, of which two dianthrones exhibited the lowest IC50 value (0.7–0.9 μM) and anthraquinones showed moderate toxicity (15–25 μM), was constructed. ConclusionUsing ML methods and in vitro screening, two classes of compounds, dianthrones and anthraquinones, were predicted and validated to have a high risk of DILI. The diparametric optimization method used in this study could provide a useful and powerful tool to screen toxicants for large datasets and is available at https://github.com/dreadlesss/Hepatotoxicity_predictor.

2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucopyranoside enhances the hepatotoxicity of emodin in vitro and in vivo

Herb-induced liver injury results from the interplay between the herb and host with the herbal components serving as the major origin for hepatotoxicity. Although Polygoni Multiflori Radix (PMR) has been frequently reported to induce liver injury, contributions of its major components such as emodin, emodin-8-O-β-D-glucopyranoside, physcion and 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucopyranoside (TSG) towards its hepatotoxicity have not been clearly identified. Our initial cytotoxicity screenings of the major PMR components using rat hepatocytes identified emodin as the most toxic. Subsequently, the bile acid homeostasis-related mechanisms of emodin and its combination treatment with TSG in PMR-associated liver injury were explored in sandwich-cultured rat hepatocytes (SCRH) and verified in rats. In SCRH, emodin was found to be able to induce total bile acid accumulation in a dose-dependent manner. In both SCRH and rats, the presence of TSG significantly enhanced the hepatotoxicity of emodin via i) increasing its hepatic exposure by inhibiting its glucuronidation mediated metabolism; ii) enhancing its disruption on bile acid homeostasis through amplifying its inhibition on bile acid efflux transporters and its up-regulation on bile acids synthesis enzymes; iii) enhancing its apoptosis. Our study for the first time demonstrated the critical role of the combination treatment with emodin and TSG in PMR-induced liver injury.

Hepatic Injury Induced by Moringa Oleifera with Rechallenge

Herb Induced Liver Injury (HILI) is a condition in which there is aggression to the liver tissue after exposure to substances present in many different medications, dietary supplements, herbs and xenobiotics.

Cover Image

The cover image is based on the Randomised Clinical Trial Corticosteroid plus glycyrrhizin therapy for chronic drug- or herb-induced liver injury achieves biochemical and histological improvements: A randomised open-label trial by Jia-Bo Wang et al., https://doi.org/10.1111/apt.16902.

Complex liver injury induced by combined Aloe Vera and vitamin A oral supplements, as assessed by histology and the updated RUCAM

A case of combined acute and chronic liver injury related to consumption of multi-ingredient nutritional oral supplements containing Aloe Vera gel and vitamin A among other vitamins, minerals and dietary elements such as fish and calamari oil in a 59-year-old female with unexplained hypertransaminasemia is reported. A unique complex liver injury was diagnosed on liver biopsy combining histological features of protracted acute hepatitis, mild manifestation of hypervitaminosis A and lipogranulomatous reaction attributed to Aloe Vera, vitamin A and lipids, respectively. Normalization of liver tests was achieved after discontinuation of all nutritional supplements. Updated Roussel Uclaf Causality Assessment Method (RUCAM) score (+8, probable) further supported herb-induced liver injury. The present case highlights the increasing incidence of complex histological liver injury linked to the constantly growing consumption of multi-ingredient dietary supplements and alternative medications.